Journal article
Polygenic risk score as a determinant of risk of non‐melanoma skin cancer in a European‐descent renal transplant cohort
American journal of transplantation, Vol.19(3), pp.801-810
03/2019
DOI: 10.1111/ajt.15057
PMCID: PMC6367067
PMID: 30085400
Abstract
Renal transplant recipients have an increased risk of non‐melanoma skin cancer (NMSC) compared to in the general population. Here, we show polygenic risk scores (PRS) calculated from genome‐wide association studies (GWAS) of NMSC in a general, nontransplant setting, can predict risk of, and time to posttransplant skin cancer. Genetic variants, reaching predefined P‐value thresholds were chosen from published squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) nontransplant GWAS. Using these GWAS, BCC and SCC PRS were calculated for each sample across three European ancestry renal transplant cohorts (n = 889) and tested as predictors of case:control status and time to NMSC posttransplant. BCC PRS calculated at P‐value threshold 1 × 10−5 was the most significant predictor of case:control status of NMSC posttransplant (OR = 1.61; adjusted P = .0022; AUC [full model adjusted for clinical predictors and PRS] = 0.81). SCC PRS at P‐value threshold 1 × 10−5 was the most significant predictor of time to posttransplant NMSC (adjusted P = 9.39 × 10−7; HR = 1.41, concordance [full model] = 0.74). PRS of nontransplant NMSC is predictive of case:control status and time to NMSC posttransplant. These results are relevant to how genomics can risk stratify patients to help develop personalized treatment regimens.
Polygenic risk score of nontransplant non‐melanoma skin cancer is predictive of case:control status and time to non‐melanoma posttransplant, demonstrating the use of genomics to stratify patients at risk for transplant complications.
Details
- Title: Subtitle
- Polygenic risk score as a determinant of risk of non‐melanoma skin cancer in a European‐descent renal transplant cohort
- Creators
- Caragh P Stapleton - Royal College of Surgeons in IrelandKelly A Birdwell - Vanderbilt University Medical CentreAmy Jayne McKnight - Queen’s University of BelfastAlexander P Maxwell - Queen’s University of BelfastPatrick B Mark - University of GlasgowM. Lee Sanders - University of IowaFiona A Chapman - University of GlasgowJessica van Setten - University Medical Centre Utrecht, Utrecht UniversityPaul J Phelan - Royal Infirmary of Edinburgh, NHS LothianClaire Kennedy - Beaumont HospitalAlan Jardine - University of GlasgowJamie P Traynor - University of GlasgowBrendan Keating - University of PennsylvaniaPeter J Conlon - Royal College of Surgeons in IrelandGianpiero L Cavalleri - Royal College of Surgeons in Ireland
- Resource Type
- Journal article
- Publication Details
- American journal of transplantation, Vol.19(3), pp.801-810
- DOI
- 10.1111/ajt.15057
- PMID
- 30085400
- PMCID
- PMC6367067
- NLM abbreviation
- Am J Transplant
- ISSN
- 1600-6135
- eISSN
- 1600-6143
- Number of pages
- 10
- Grant note
- Northern Ireland Kidney Research Fund Irish Research Council (EPSPG2015) Punchestown Kidney Research Fund (EPSPG2015) Science Foundation Ireland (15/IA/3152) NHS Research Scotland (Career Research Fellowship)
- Language
- English
- Date published
- 03/2019
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984094339702771
Metrics
73 Record Views